Abstracts

Rationale: The identification of a structural and functional network of seizure propagation in epilepsy is of interest to both clinicians and researchers. We previously [1] identified a network of regions where functional connectivity (FC) was correlated with gray matter concentration in temporal lobe epilepsy (TLE) patients, but not in healthy controls. This suggests that these are nodes in the seizure pathway that may experience slow structural and functional changes over time. These regions have also been implicated in other studies of TLE, but not exclusively in a single network. The goal of this study is to investigate functional changes over time within the proposed network including the left and right hippocampus, left and right thalamus, precuneus and the mid cingulate region in TLE.Methods: We enrolled 7 subjects with TLE and 7 age and gender matched healthy controls in an ongoing study. The TLE patients had unilateral hippocampal seizure origin using standard clinical assessments including video-EEG, MRI and PET. Structural and functional imaging (80x80, FOV = 240 mm, 34 axial slices, TE = 35 ms, TR = 2 sec, slice thickness = 3.5 mm/ 0.5 mm gap, 600 volumes) were performed on a 3T MRI scanner. After slice timing and motion correction and physiological noise regression, spatial normalization to the MNI template was performed. The regions named above were identified in each individual and FC was calculated as the linear correlation between average time series, after regressing motion, white matter and CSF.Results: We report three main findings. First, the FC between hippocampi is decreased in TLE compared to age and gender matched controls (p=0.010). The average volume across the two hippocampi is also significantly reduced in the patients (p=0.007). Furthermore, there is a significant linear correlation between the average volume of the hippocampi and the FC across both groups (p=0.034), but not in each individual group. Second, we observe that the data thus far also replicates our earlier finding [2] of linearly increasing cross hippocampal connectivity in TLE after 10 years of disease duration (Fig 1). Third, this connectivity trend is also found (opposite in sign) in the FC between the left and right thalami and the mid cingulate region in patients (Fig 2), but not in controls. Specifically, FC between the hippocampi is negatively correlated with the FC between the left and right thalami and the mid cingulate region (p=0.0051) in TLE, but not controls. Conclusions: These data suggest an evolution occurring across the proposed TLE seizure network. Our results show that the pathway of spread between the thalami and the frontal lobes, thought to involve the mid cingulate region, evolves in synchrony with the hippocampal pathway as the disease progresses. We propose that elucidating the evolution of this network could be useful in the prediction of long and short term outcome of surgical therapy in these patients. NIH R01 NS055822 and NS075270 (Morgan) [1] Holmes, MJ et al. Brain Connectivity 2013; 3(1):22. [2] Morgan, VL et al. Epilepsia 2011;52(9):1741.